Role of the Metalloproteinase-7 (181A>G) Polymorphism in Gastric Cancer Susceptibility: A Case Control Study in Kashmir Valley

Abstract

Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificityagainst extracellular matrix (ECM) and non-ECM components. A promoter polymorphism MMP-7 181A>Gis known to modify the gene transcription activity of the proteinase gene and influence susceptibility to variouscancers. The present case-control study comprising 108 gastric cancer (GC) patients and 195 healthy controlswas carried out to determine any association of this polymorphism in the Kashmir valley where the GC incidenceis very high. Genotypic data were statistically analyzed by logistic regression models. In combined analysis,homozygous variant GG genotype of MMP-7 (-181A>G) polymorphism was associated with a more than twofold increased risk of GC (OR=2.13; 95% CI =1.13-4.01; p=0.020; P-trend=0.01) compared with the commonAA genotype and the data fitted a recessive model. After sub-grouping based on tumor histology, the risk wasmore pronounced with squamous cell histology (OR=9.34; 95% CI =1.97-44.33; p=0.005) as compared toadenocarcinoma. The cancer risk due to smoking or high intake of salted tea was not influenced by the MMP-7 polymorphism. In conclusion, results from present study suggest that common MMP-7 (181A>G) geneticpolymorphism may contribute to squamous cell gastric cancer susceptibility in the Kashmir valley.